Age of Diagnosis Does Not Alter the Presentation or Progression of Robustly Defined Adult-Onset Type 1 Diabetes
Authors: Nicholas J. Thomas, Anita V. Hill, Colin M. Dayan, Richard A. Oram, Timothy J. McDonald, Beverley M. Shields, Angus G. Jones, Godwin Simon, Angelo Ramos, Andrea Norris, Kai Tan, Parth Narendran, Shenaz Ramtoola, Amar Ali, Moulinath Banerjee, Augustin Brooks, Ali Chakera, Andrew Johnson, Danijela Tatovic, Chitrabhanu Ballav, Colin Dayan, Sunil Nair, Francis Game, Susan Beames, Gerry Rayman, Marie Snell, Susie Butler, Sarah Beck, Janet Beecham, John Wilding, Sam Rice, Mimi Chen, Athinyaa Thiraviaraj, Siva Sivappriyan, Basil Issa, Asif Humayun, Rebecca Hinch, Leena Krishnan, Khin Swe Myint, Charles Fox, Jennifer Prouten, Mike Sampson, Peter Mansell, Carolyn Chee, Katherine Owen, Ioannis Dimitropoulis, Michael Cummings, Foteini Kavourra, Adrian Heald, Simon Heller, Sarbpreet Sihota, Vakkat Muraleedharan, Tara Watson, Hermione Price, Roger Whittaker, Sarah Orme, Ben Field, Stephen Bain, Beas Battacharya, Lesley Haxton, Suzannah Pegler, Catherine Thompson, Rob Andrew, Jamie Smith, Duncan Browne, Steve Creely, Rahul Yadav, Rakhi Kakad, Ken Laji, Mohit Kumar, Alirezi Mohammadi, James Young, Seshadri Pramodh, Vijay Jayagopal, Angus Jones, Anita Hill, Robert Bolt, Suzanne Hammersley, Migaila Aldred, Anna Steele, Peter Tippett
Journal: Diabetes Care (2023)

OBJECTIVE To determine whether presentation, progression, and genetic susceptibility of robustly defined adult-onset type 1 diabetes (T1D) are altered by diagnosis age. RESEARCH DESIGN AND METHODS We compared the relationship between diagnosis age and presentation, C-peptide loss (annual change in urine C-peptide–creatinine ratio [UCPCR]), and genetic susceptibility (T1D genetic risk score [GRS]) in adults with confirmed T1D in the prospective StartRight study, 1,798 adults with new-onset diabetes. T1D was defined in two ways: two or more positive islet autoantibodies (of GAD antibody, IA-2 antigen, and ZnT8 autoantibody) irrespective of clinical diagnosis (n = 385) or one positive islet autoantibody and a clinical diagnosis of T1D (n = 180). RESULTS In continuous analysis, age of diagnosis was not associated with C-peptide loss for either definition of T1D (P &amp;gt; 0.1), with mean (95% CI) annual C-peptide loss in those diagnosed before and after 35 years of age (median age of T1D defined by two or more positive autoantibodies): 39% (31–46) vs. 44% (38–50) with two or more positive islet autoantibodies and 43% (33–51) vs. 39% (31–46) with clinician diagnosis confirmed by one positive islet autoantibody (P &amp;gt; 0.1). Baseline C-peptide and T1D GRS were unaffected by age of diagnosis or T1D definition (P &amp;gt; 0.1). In T1D defined by two or more autoantibodies, presentation severity was similar in those diagnosed before and after 35 years of age: unintentional weight loss, 80% (95% CI 74–85) vs. 82% (76–87); ketoacidosis, 24% (18–30) vs. 19% (14–25); and presentation glucose, 21 mmol/L (19–22) vs. 21 mmol/L (20–22) (all P ≥ 0.1). Despite similar presentation, older adults were less likely to be diagnosed with T1D, insulin-treated, or admitted to hospital. CONCLUSIONS When adult-onset T1D is robustly defined, the presentation characteristics, progression, and T1D genetic susceptibility are not altered by age of diagnosis.